PROJECT SUMMARY/ ABSTRACT Parents serve as co-regulators for their young children, helping them regulate behaviors, emotions, and physiology and supporting the development of healthy brain circuitry. Neglecting parents often fail to serve as co-regulators, which has implications for young children?s self-regulatory capabilities and brain development. As children become older, these difficulties with self-regulation may become more pronounced. Adolescence represents a period of particular vulnerability for the emergence of mental health problems because of increasing demands for regulation of emotions and behaviors, coupled with on-going development of neural circuits that support emotional and behavioral regulation. In this competing renewal, we propose to follow children into adolescence who initially participated in a randomized clinical trial design of Attachment and Biobehavioral Catch-up (ABC) as infants, allowing us to experimentally assess plasticity and modification of brain circuits and self-regulation as the result of an early intervention. The ABC intervention was designed to help parents learn to interact in responsive and sensitive ways, with the expectation that children would show enhanced ability to regulate behavior, emotions, and physiology. We assessed the efficacy of the ABC intervention among parents involved with Child Protective Services (CPS). Parents were randomized to ABC or to a control intervention. Children were followed at T1 (ages 1-4) and T2 (ages 8-10). At T1, more of the children in the ABC group developed secure and organized attachments than children in the DEF group, and children in ABC showed more normative production of cortisol, less expression of negative emotions, and stronger inhibitory control than children in DEF. ABC parents were more sensitive and showed more optimal neural activity than DEF parents. At T2, ABC children showed greater prefrontal cortex activation in response to photographs of fearful faces than DEF children, suggesting better regulation to threat at the level of brain activation. Also at T2, children in the ABC group reported more secure relationships with parents, and showed more normative cortisol production and more optimal autonomic nervous system functioning than DEF children. In adolescence, the ABC intervention is expected to result in enhanced brain circuitry and more optimal functioning relative to the control intervention. In the proposed study, we will assess behavioral and neurobiological development among 13-, 14- and 15-year-old adolescents whose parents were referred by CPS to a randomized clinical trial in infancy (n=120), and among low-risk adolescents followed since middle childhood (n=80). At each annual assessment, the primary constructs, inhibitory control, emotion regulation, physiological regulation, and attachment/affiliation, will be assessed at the level of brain activation and circuitry, and at the behavioral level.